These authors contributed equally to this work.
Hypoxia-inducible MicroRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma†
Article first published online: 30 NOV 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 6, pages 2064–2075, December 2011
How to Cite
Ying, Q., Liang, L., Guo, W., Zha, R., Tian, Q., Huang, S., Yao, J., Ding, J., Bao, M., Ge, C., Yao, M., Li, J. and He, X. (2011), Hypoxia-inducible MicroRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology, 54: 2064–2075. doi: 10.1002/hep.24614
Potential conflict of interest: Nothing to report.
This work was supported by grants from the National Natural Science foundation of China (81071637, to X.H; 91029728, to X.H; 81101587, to L.L), the Science and Technology Commission of Shanghai Municipality (10JC1414200, to X.H; 11XD1404500, to X.H), the Shanghai Municipal Bureau of Public Health (2007088, to L.L), and the Shanghai Rising-star Program Funds (11QA1406200, to L.L).
- Issue published online: 30 NOV 2011
- Article first published online: 30 NOV 2011
- Accepted manuscript online: 16 AUG 2011 03:36PM EST
- Manuscript Accepted: 5 AUG 2011
- Manuscript Received: 25 MAY 2011
As the “master” microRNA that is induced by hypoxia, miR-210 is involved in multiple processes in the hypoxia pathway. However, whether miR-210 mediates hypoxia-induced tumor cell metastasis still remains unclear. Here, we demonstrate that miR-210 is frequently up-regulated in hepatocellular carcinoma (HCC) samples and promotes the migration and invasion of HCC cells. Furthermore, miR-210 can be induced by hypoxia in HCC cells and mediates hypoxia-induced HCC cell metastasis. We identify vacuole membrane protein 1 (VMP1) as the direct and functional downstream target of miR-210; in addition, we show that its expression is negatively correlated with the expression of miR-210 in HCC. Intriguingly, VMP1 is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia-induced HCC cell metastasis. Conclusion: These findings extend our understanding of the function of miR-210 in the hypoxia pathway, and this newly identified hypoxia/miR-210/VMP1 pathway should facilitate the development of novel therapeutics against hypoxic tumor cells. (HEPATOLOGY 2011)